Trends in Neurosciences

Experimental evidence for sparse firing in the neocortex.

Publication Date: 2012 May 12 PMID: 22579264
Authors: Barth, A. L. - Poulet, J. F.
Journal: Trends Neurosci

The advent of unbiased recording and imaging techniques to evaluate firing activity across neocortical neurons has revealed substantial heterogeneity in response properties in vivo, and that a minority of neurons are responsible for the majority of spikes. Despite the computational advantages to sparsely firing populations, experimental data defining the fraction of responsive neurons and the range of firing rates have not been synthesized. Here we review data about the distribution of activity across neuronal populations in primary sensory cortex. Overall, the firing output of granular and infragranular layers is highest. Although subthreshold activity across supragranular neurons is decidedly non-sparse, spikes are much less frequent and some cells are silent. Superficial layers of the cortex may employ specific cell and circuit mechanisms to increase sparseness.

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Mitochondria as a central sensor for axonal degenerative stimuli.

Publication Date: 2012 May 10 PMID: 22578891
Authors: Court, F. A. - Coleman, M. P.
Journal: Trends Neurosci

Axonal degeneration is a major contributor to neuronal dysfunction in many neurological conditions and has additional roles in development. It can be triggered by divergent stimuli including mechanical, metabolic, infectious, toxic, hereditary and inflammatory stresses. Axonal mitochondria are an important convergence point as regulators of bioenergetic metabolism, reactive oxygen species (ROS), Ca(2+) homeostasis and protease activation. The challenges likely to render axonal mitochondria more vulnerable than their cellular counterparts are reviewed, including axonal transport, replenishing nuclear-encoded proteins and maintenance of quality control, fusion and fission in locations remote from the cell body. The potential for mitochondria to act as a decision node in axon loss is considered, highlighting the need to understand the biology of axonal mitochondria and their contributions to degenerative mechanisms for novel therapeutic strategies.

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Sensitive time-windows for susceptibility in neurodevelopmental disorders.

Publication Date: 2012 Apr 25 PMID: 22542246
Authors: Meredith, R. M. - Dawitz, J. - Kramvis, I.
Journal: Trends Neurosci

Many neurodevelopmental disorders (NDDs) are characterized by age-dependent symptom onset and regression, particularly during early postnatal periods of life. The neurobiological mechanisms preceding and underlying these developmental cognitive and behavioral impairments are, however, not clearly understood. Recent evidence using animal models for monogenic NDDs demonstrates the existence of time-regulated windows of neuronal and synaptic impairments. We propose that these developmentally-dependent impairments can be unified into a key concept: namely, time-restricted windows for impaired synaptic phenotypes exist in NDDs, akin to critical periods during normal sensory development in the brain. Existence of sensitive time-windows has significant implications for our understanding of early brain development underlying NDDs and may indicate vulnerable periods when the brain is more susceptible to current therapeutic treatments.

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EphBs: an integral link between synaptic function and synaptopathies.

Publication Date: 2012 May PMID: 22516618
Authors: Sheffler-Collins, S. I. - Dalva, M. B.
Journal: Trends Neurosci

The assembly and function of neuronal circuits rely on selective cell-cell interactions to control axon targeting, generate pre- and postsynaptic specialization and recruit neurotransmitter receptors. In neurons, EphB receptor tyrosine kinases mediate excitatory synaptogenesis early during development, and then later coordinate synaptic function by controlling synaptic glutamate receptor localization and function. EphBs direct synapse formation and function to regulate cellular morphology through downstream signaling mechanisms and by interacting with glutamate receptors. In humans, defective EphB-dependent regulation of NMDA receptor (NMDAR) localization and function is associated with neurological disorders, including neuropathic pain, anxiety disorders and Alzheimer's disease (AD). Here, we propose that EphBs act as a central organizer of excitatory synapse formation and function, and as a key regulator of diseases linked to NMDAR dysfunction.

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MicroRNAs in neuronal function and dysfunction.

Publication Date: 2012 May PMID: 22436491
Authors: Im, H. I. - Kenny, P. J.
Journal: Trends Neurosci

MicroRNAs (miRNAs) are small noncoding RNA transcripts expressed throughout the brain that can regulate neuronal gene expression at the post-transcriptional level. Here, we provide an overview of the role for miRNAs in brain development and function, and review evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction. A better understanding of how miRNAs influence the development of neuropsychiatric disorders may reveal fundamental insights into the causes of these devastating illnesses and offer novel targets for therapeutic development.

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Does moderate drinking harm the fetal brain? Insights from animal models.

Publication Date: 2012 May PMID: 22402065
Authors: Valenzuela, C. F. - Morton, R. A. - Diaz, M. R. - Topper, L.
Journal: Trends Neurosci

Although public health campaigns advise pregnant women to abstain from ethanol, drinking during pregnancy is pervasive. Here, we highlight recent studies that have clearly demonstrated long-lasting neurobehavioral deficits in the offspring of laboratory animals exposed to moderate levels of ethanol during development. Alterations in learning, memory, motor coordination, social behavior, and stress responses were identified in these animals. Increased vulnerability to substance abuse was also demonstrated. These behavioral alterations have been associated with impairments in neurotransmitter systems, neuromodulators, and/or synaptic plasticity in several brain regions. With this review we hope to contribute to a better appreciation of the potential effects of developmental exposure to moderate ethanol levels, leading to better interventions aimed at relieving fetal alcohol spectrum disorders.

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Sculpting the hippocampus from within: stress, spines, and CRH.

Publication Date: 2012 May PMID: 22386641
Authors: Maras, P. M. - Baram, T. Z.
Journal: Trends Neurosci

Learning and memory processes carried out within the hippocampus are influenced by stress in a complex manner, and the mechanisms by which stress modulates the physiology of the hippocampus are not fully understood. This review addresses how the production and release of the neuropeptide corticotropin-releasing hormone (CRH) within the hippocampus during stress influences neuronal structure and hippocampal function. CRH functions in the contexts of acute and chronic stresses taking place during development, adulthood and aging. Current challenges are to uncover how the dynamic actions of CRH integrate with the well-established roles of adrenal-derived steroid stress hormones to shape the cognitive functions of the hippocampus in response to stress.

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Memory enhancement: consolidation, reconsolidation and insulin-like growth factor 2.

Publication Date: 2012 May PMID: 22341662
Authors: Alberini, C. M. - Chen, D. Y.
Journal: Trends Neurosci

Life and societies would change significantly if memory capacity or persistence in health and disease could be enhanced. It has been known for many years that memory can be improved and strengthened. Substances known to enhance memory include hormones, neurotransmitters, neuropeptides and metabolic substrates. Recently, attention has been given to identifying the molecular mechanisms and targets whereby memory enhancement can be achieved. One approach would be to target the physiological changes that are induced by learning and naturally required for memory strengthening via consolidation and reconsolidation. Here, we review approaches that boost memories by targeting the cAMP response element binding protein-CCAAT enhancer binding protein (CREB-C/EBP) pathway and/or its recently identified target gene insulin-like growth factor 2 (IGF2).

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Emerging roles of the neuronal nucleolus.

Publication Date: 2012 May PMID: 22305768
Authors: Hetman, M. - Pietrzak, M.
Journal: Trends Neurosci

Although, the nucleolus has been observed for almost 200 years in neurons, studies that directly address the neuronal roles of this subnuclear structure have appeared only recently. The aim of this review is to discuss recent progress and identify some critical questions that remain to be answered. As expected for the cellular center of ribosome biogenesis, the nucleolus is essential for the growth of developing neurons, including neurite morphogenesis and long-term maintenance of mature neurons. In addition, the nucleolus contributes to neuronal stress responses, including the regulation of apoptosis. Hence, disrupted neurodevelopment or neurodegeneration are among the likely consequences of nucleolar dysfunction. Conversely, the presence of active nucleoli may determine the potential for neurorepair.

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